M. Ahmad Chaudhry

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M. Ahmad Chaudhry is an American radiologist, Associate Professor at the University of Vermont, and Interim Associate Dean for Research, in the College of Nursing and Health Sciences. [1]

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He received a Ph.D. degree in molecular biology from the University of Manchester, UK. He did postdoctoral research work at the University of Alberta in Canada, before joining the University of Pennsylvania as a Senior Research Investigator. His research interests are micro-RNA responses to radiation exposure, radiation-induced bystander effect, cell cycle perturbations and the enzymatic processing of clustered DNA damage.

Education

He received his M.Sc. from University of Manchester, UK, Molecular Biology, 1987 and his Ph.D., University of Manchester, UK, Molecular Biology, 1990.

The role of micro-RNA in the cellular response to radiation treatment

Ionizing radiation interferes with cellular functions at all levels of cell organization. The ionizing radiation-induced stress response is very complex and involves many cellular processes. Dr. Chaudry is investigating the involvement of small non-coding micro-RNA in the response of human cells exposed to ionizing radiation. Micro RNAs (miRNAs) are small non-protein-coding single-stranded RNAs of ~22 nucleotides that function as negative gene regulators. miRNA negatively regulate their targets either by binding with perfect or nearly perfect complementarity to protein coding mRNA sequences to induce the RNA-mediated interference (RNAi) pathway. Most miRNAs do not cleave their mRNA targets as a mechanism of gene regulation. These miRNAs bind to imperfect complementary sites within the 3′ untranslated regions (UTRs) of their mRNA targets. In this case the target-gene repression occurs post-transcriptionally at the level of translation resulting in reduced protein levels but the mRNA levels remain unaffected. A single miRNA has the capability to bind to as many as 200 diverse gene targets ranging from transcription factors, secreted factors, receptors and transporters, thus potentially controlling the expression of about one-third of human mRNAs. Research has identified cell type specific modulation of several miRNA in gamma radiation and X-ray-treated human cells. Other studies from our laboratory showed that the expression of many miRNA markedly differ within the same cell line after exposure to either low or high doses of radiation. His work also identified radiation-induced modulation of miRNA in cells with altered DNA repair capability. These studies have provided evidence that miRNA are involved in the response to ionizing radiation exposure in human cells.

Selected publications

Related Research Articles

microRNA Small non-coding ribonucleic acid molecule

MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in mRNA molecules, then silence said mRNA molecules by one or more of the following processes:

  1. Cleavage of the mRNA strand into two pieces,
  2. Destabilization of the mRNA by shortening its poly(A) tail, or
  3. Reducing translation of the mRNA into proteins.
<span class="mw-page-title-main">Gene expression</span> Conversion of a genes sequence into a mature gene product or products

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. The process of gene expression is used by all known life—eukaryotes, prokaryotes, and utilized by viruses—to generate the macromolecular machinery for life.

<span class="mw-page-title-main">Regulation of gene expression</span> Modifying mechanisms used by cells to increase or decrease the production of specific gene products

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

<span class="mw-page-title-main">DNA repair</span> Cellular mechanism

DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur. This can eventually lead to malignant tumors, or cancer as per the two-hit hypothesis.

<span class="mw-page-title-main">Molecular lesion</span> Damage to the structure of a biological molecule

A molecular lesion or point lesion is damage to the structure of a biological molecule such as DNA, RNA, or protein. This damage may result in the reduction or absence of normal function, and in rare cases the gain of a new function. Lesions in DNA may consist of breaks or other changes in chemical structure of the helix, ultimately preventing transcription. Meanwhile, lesions in proteins consist of both broken bonds and improper folding of the amino acid chain. While many nucleic acid lesions are general across DNA and RNA, some are specific to one, such as thymine dimers being found exclusively in DNA. Several cellular repair mechanisms exist, ranging from global to specific, in order to prevent lasting damage resulting from lesions.

Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor.

<span class="mw-page-title-main">Heterogeneous ribonucleoprotein particle</span>

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm. Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation.

<span class="mw-page-title-main">Microprocessor complex subunit DGCR8</span> Protein-coding gene in the species Homo sapiens

The microprocessor complex subunit DGCR8(DiGeorge syndrome critical region 8) is a protein that in humans is encoded by the DGCR8 gene. In other animals, particularly the common model organisms Drosophila melanogaster and Caenorhabditis elegans, the protein is known as Pasha. It is a required component of the RNA interference pathway.

<span class="mw-page-title-main">HMGA2</span> Protein-coding gene in the species Homo sapiens

High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the HMGA2 gene.

<span class="mw-page-title-main">DNA-PKcs</span> Protein-coding gene in the species Homo sapiens

DNA-dependent protein kinase catalytic subunit, also known as DNA-PKcs, is an enzyme that plays a crucial role in repairing DNA double-strand breaks and has a number of other DNA housekeeping functions. In humans it is encoded by the gene designated as PRKDC or XRCC7. DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase protein family. The DNA-Pkcs protein is a serine/threonine protein kinase consisting of a single polypeptide chain of 4,128 amino acids.

<span class="mw-page-title-main">ERCC1</span> Protein-coding gene in the species Homo sapiens

DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

<span class="mw-page-title-main">DNA polymerase beta</span> Protein-coding gene in the species Homo sapiens

DNA polymerase beta, also known as POLB, is an enzyme present in eukaryotes. In humans, it is encoded by the POLB gene.

<span class="mw-page-title-main">RAD52</span> Protein-coding gene in the species Homo sapiens

RAD52 homolog , also known as RAD52, is a protein which in humans is encoded by the RAD52 gene.

Post-transcriptional regulation is the control of gene expression at the RNA level. It occurs once the RNA polymerase has been attached to the gene's promoter and is synthesizing the nucleotide sequence. Therefore, as the name indicates, it occurs between the transcription phase and the translation phase of gene expression. These controls are critical for the regulation of many genes across human tissues. It also plays a big role in cell physiology, being implicated in pathologies such as cancer and neurodegenerative diseases.

miR-155 Non-coding RNA in the species Homo sapiens

MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases.

<span class="mw-page-title-main">Cancer epigenetics</span> Field of study in cancer research

Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.

<span class="mw-page-title-main">MIR34A</span> Non-coding RNA in the species Homo sapiens

MicroRNA 34a (miR-34a) is a microRNA that in humans is encoded by the MIR34A gene.

Ionizing radiation can cause biological effects which are passed on to offspring through the epigenome. The effects of radiation on cells has been found to be dependent on the dosage of the radiation, the location of the cell in regards to tissue, and whether the cell is a somatic or germ line cell. Generally, ionizing radiation appears to reduce methylation of DNA in cells.

Pharmacoepigenetics is an emerging field that studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment.

Epigenetic effects of smoking concerns how epigenetics contributes to the deleterious effects of smoking. Cigarette smoking has been found to affect global epigenetic regulation of transcription across tissue types. Studies have shown differences in epigenetic markers like DNA methylation, histone modifications and miRNA expression between smokers and non-smokers. Similar differences exist in children whose mothers smoked during pregnancy. These epigenetic effects are thought to be linked to many of negative health effects associated with smoking.

References

  1. "College of Nursing and Health Sciences : University of Vermont". 2012-10-13. Archived from the original on 13 October 2012. Retrieved 2024-02-16.